Department of Paediatrics and Nephrology, Medical University of Białystok, ul. Waszyngtona 17, Białystok, Poland.
Pediatr Nephrol. 2010 May;25(5):889-97. doi: 10.1007/s00467-009-1397-1.
The aim of work was to investigate whether serum and urinary neutrophil gelatinase-associated lipocalin(sNGAL and uNGAL, respectively) are potential biomarkers of early cyclosporine A (CsA) nephrotoxicity in steroid-dependent nephrotic children (SDNS). The study group (I) consisted of 19 children with SDNS aged 9.46+/-5.52 years treated with CsA. The children were examined four times: at proteinuria relapse, prior to CsA treatment,then after 3, 6, and 12 months of CsA treatment. The control group (II) consisted of 18 healthy children aged 3-15 years. A commercial enzyme-linked immunosorbent assay method was used to measure NGAL concentration.The sNGAL level in SDNS children prior to the administration of CsA was similar to that in the healthy controls (p>0.05), but it increased significantly during the course of treatment (p<0.01). The uNGAL/creatinine (cr) ratio in SDNS patients was higher before the withdrawal of CsA therapy (p<0.05), and was also increased at the consecutive examinations (p<0.01). There was a positive correlation between both sNGAL and uNGAL levels and CsA serum level. However, based on the serum and urinary NGAL/cr receiver operating characteristic curve and area under the curve (AUC) analysis, it remains uncertain whether uNGAL is a good predictor of cyclosporine nephropathy. Both sNGAL and uNGAL concentrations increased during the course of CsA treatment. Further studies in larger groups of patients are therefore necessary to confirm our experimental data that increased NGAL levels may be a non-invasive marker for the early detection of tubulointerstitial damage in CsA nephrotoxicity.
研究血清和尿中性粒细胞明胶酶相关脂质运载蛋白(sNGAL 和 uNGAL)是否分别为激素依赖型肾病综合征(SDNS)儿童环孢素 A(CsA)早期肾毒性的潜在生物标志物。研究组(I)包括 19 名 9.46±5.52 岁的 SDNS 患儿,给予 CsA 治疗。患儿共进行了 4 次检查:蛋白尿复发时、CsA 治疗前、治疗后 3、6、12 个月。对照组(II)包括 18 名 3-15 岁的健康儿童。采用商业酶联免疫吸附测定法测量 NGAL 浓度。SDNS 患儿在给予 CsA 之前的 sNGAL 水平与健康对照组相似(p>0.05),但在治疗过程中明显升高(p<0.01)。SDNS 患者在停用 CsA 治疗前的 uNGAL/肌酐(cr)比值较高(p<0.05),连续检查时也升高(p<0.01)。sNGAL 和 uNGAL 水平与 CsA 血清水平呈正相关。然而,基于血清和尿液 NGAL/cr 接收者操作特征曲线和曲线下面积(AUC)分析,uNGAL 是否是环孢素肾病的良好预测指标仍不确定。在 CsA 治疗过程中,sNGAL 和 uNGAL 浓度均增加。因此,需要进一步在更大的患者群体中进行研究,以证实我们的实验数据,即增加的 NGAL 水平可能是早期发现 CsA 肾毒性肾小管间质损伤的非侵入性标志物。